title: Upregulated miR-155 in papillary thyroid carcinoma promotes tumor growth by targeting APC and activating Wnt/β-catenin signaling.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are strongly implicated in many cancers, including papillary thyroid carcinoma (PTC), which is the most common malignancy in thyroid tissue. Recently, miRNA-155 (miR-155) has been proved to play a substantial role in liposarcoma and breast cancer, but its functions in the context of PTC remain unknown.
  
  
  OBJECTIVE
  The objective was to investigate the potential involvement of miR-155 in PTC.
  
  
  METHODS
  Expression levels of miR-155 were assessed via quantitative real-time PCR in 20 pairs of human PTC and adjacent normal tissues and in 4 human PTC cell lines. Lentiviral miR-155 overexpression models were performed in TPC-1 and CGTH-W3 cells, and the effects on cell growth were evaluated. We have searched for miR-155 targets and identified the hypothesis that miR-155 could promote tumor growth of PTC by targeted regulation of adenomatous polyposis coli (APC) expression and activating the Wnt/β-catenin signaling.
  
  
  RESULTS
  MiR-155 levels were markedly increased in PTC specimens and PTC cell lines. Overexpression of miR-155 dramatically promoted PTC cell viability and colony formation in vitro, whereas miR-155 depletion reduced these parameters. Further studies revealed that APC is a novel miR-155 target, because miR-155 bound directly to its 3'-untranslated region and reduced both the mRNA and protein levels of APC. Similar to the miR-155 over-expression, APC downregulation promoted cell growth, whereas rescued APC expression reversed the promotive effect of miR-155. Furthermore, miR-155 overexpression resulted in activation of β-catenin and induction of several downstream genes including c-Myc, cyclin D1, TCF-1. and LEF-1. Depletion of β-catenin partially prevented miR-155-induced tumor cell viability and colony formation. In xenograft animal experiments, we found overexpressed miR-155 effectively promoted tumor growth of PTC cells.
  
  
  CONCLUSIONS
  Our results indicate that miR-155 functions as an oncogene in PTC. By targeting APC, miR-155 efficiently regulates the Wnt/β-catenin signaling. And miR-155 may be a potential therapeutic or diagnostic/prognostic target for treating PTC.
authors.affiliation: Department of Nuclear Medicine, Shanghai 10th People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhang
authors.forename: Maoquan
authors.initials: M
authors.lastname: Li
authors.forename: Keqiang
authors.initials: K
authors.lastname: Zuo
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.forename: Meng
authors.initials: M
authors.lastname: Ye
authors.forename: Lanbao
authors.initials: L
authors.lastname: Ding
authors.forename: Haidong
authors.initials: H
authors.lastname: Cai
authors.forename: Da
authors.initials: D
authors.lastname: Fu
authors.forename: Youben
authors.initials: Y
authors.lastname: Fan
authors.forename: Zhongwei
authors.initials: Z
authors.lastname: Lv
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D002277:Carcinoma / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D002291:Carcinoma, Papillary; D049109:Cell Proliferation; D017491:Genes, APC; D006801:Humans; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D015854:Up-Regulation; D060449:Wnt Signaling Pathway / Q000502:physiology*; D051176:beta Catenin / Q000502:physiology*
chemical_list: D020413:3' Untranslated Regions; C495270:CTNNB1 protein, human; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D051176:beta Catenin